Over the past decade, several proteins have been identified that affect the multi-cell lineage differentiation of hematopoietic cells. These proteins cause a common set of pluripotent stem cells, which reside predominantly in the bone marrow, to differentiate into red cells, neutrophils, basophils, eosinophils, monocytes, platelets, and lymphocytes. Such proteins were initially identified by their ability to support clonal growth of hematopoietic progenitor cells in semisolid media, and as a result they are referred to as hematopoietic colony-stimulating factors, or CSFs.
In those systems which have been most studied, human and mouse, CSFs have been identified and characterized by the types of cells whose differentiation and proliferation they appear to enhance. Two CSFs are relatively lineage specific, and have ascribed to them the names of the cells that they produce. For instance, granulocyte-CSF (G-CSF) generates mostly neutrophilic granulocytes, and macrophage CSF (M-CSF) generates largely macrophages. In contrast to these two CSF's, multi-CSF (also known as interleukin-3 or IL-3) produces colonies composed of many different cell lineages. Lastly, granulocyte-macrophage-CSF (GM-CSF) effects the production of neutrophilic granulocytes, macrophages, and eosinophils, as well as other cell types. It is thought that G-CSF and M-CSF are responsible for the growth and proliferation of temporaxily late progenitor cells already committed to the production of granulocytes, and macrophages, respectively. In contrast, GM-CSF is thought to interact with progenitor cells produced early during hematopoiesis that are capable of differentiating into several different cell types; neutrophils, eosinophils, or monocytes. Similarly, the multiplicity of activities attributable to IL-3 is believed to be a result of its capacity to support the growth of cells from relatively early pluripotent progenitor cells to mature hematopoietic cells of different lineages.
Because CSFs are thought to have significant clinical applications, considerable effort has been expended to identify sources of CSFs, and to develop ways of purifying the molecules from bodily fluids or cell culture supernatants, where they may be present at very low levels. Consequently, in order to increase the mounts of CSFs available for clinical studies, the DNA sequences that encode the various CSFs have now been identified, cloned into suitable expression vehicles, and the recombinant proteins generated therefrom characterized with regard to their physical properties and their biological activities. Concomitantly, antibodies have been, and continue to be generated that react with the various CSFs that can be used as tools to facilitate their isolation and purification, as well as having therapeutic or diagnostic applications.